The present invention relates to the field of examination and analysis of living tissues, and has for its object a process for the detection and mapping of inflamed zones of living tissues, as well as a device to practice the same.
The term xe2x80x9cinflammationxe2x80x9d generally designates, and particularly in the present case, all the processes developed by living organisms in response to an aggression of internal or external origin.
Inflammation gives rise to the major cellular histocompatibility system comprising leukocytes, lymphocytes, monocytes, histocytes, macrophages, etc . . . , as well as their secretion products such as prostaglandins, histamines, serotonins and cytokines (interferons, interleukins, tumoral necrosis factors . . . ).
It is already known to use the fluorescence of an exogensis chromophore of the type derived from hematoporphyrin or of the precursor type of protoporphyrine IX (5-amino-levulinic acid) to detect inflammatory or cancerous lesions.
Thus, it has been shown that these exogenous chromophores, concentrate, after injection, more particularly in the inflammatory or cancerous lesions.
Moreover, there are also known methods for the detection of cancers based on emission of autofluorescence in the spectral band of blue light.
In these latter methods, one takes account of the endogenous chromophores derived from nicotinamides (NAD, NADH), or constituting an extracellular matrix such as collagens, elastins or flavin derivatives.
Moreover, the presence of porphyrins in tissues has been known since 1920. It has been observed in tumors, and then in the Harder gland (located behind the eye muscles) of rodents and finally in very small quantity in normal tissues. It is principally protoporphyrin IX synthesized in cells from 5-amino-levulinic acid, that is the first step of the synthesis of hemoglobin.
The reason for the presence of this enzymatic path (normally expressed in the bone marrow) in normal or tumorous tissues, remains for the moment unknown, although it has recently been shown that this synthesis is under the control of certain hypophysary hormones.
However, the inventors of the present invention have discovered, in an unexpected and surprising manner, the presence of an abnormally high quantity of porphyrins in numerous situations whose common character is the existence of an inflammation. Present at very low levels in healthy tissues which have been studied (muscles, esophagus, pancreas and liver, at a slightly higher level in this latter, the site of partial destruction of the red corpuscles), these endogenous porphyrins become very abundant in these same tissues after aggression by a trauma (muscle), an irritating product (liver), by the development of a cancer (esophagus, pancreas) or an acute or chronic experimental pancreatitis.
The present invention has for its present object a process for the detection and mapping of inflamed zones of living tissues, characterized in that it consists in subjecting the tissues to be analyzed to a luminous excitation in a predetermined spectral field, acquiring at least the unprocessed fluorescence signal of the porphyrins for a plurality of points of measurement, and determining, for each point of measurement, at least the intensity of fluorescence for wavelengths characteristic of endogenous porphyrins.
The invention also has for its object a device for practicing the mentioned process, principally constituted by a luminous excitation unit of low intensity in the spectral bands centered about 400 nm and about 590 nm, a filtering module comprising a set of pass-band filters adapted to select fluorescenses specific to the different chromophores in question, a unit for detection and recordation of images of the fluorescence of the surface of the examined tissues and, finally, a data unit for processing point by point, or pixel by pixel, of the images recovered and the command and control of the assembly of the device, associated with storage and edition means for images.